Journal
JOURNAL OF ENDOCRINOLOGY
Volume 221, Issue 2, Pages 253-260Publisher
BIOSCIENTIFICA LTD
DOI: 10.1530/JOE-13-0504
Keywords
insulin; fetus; primate; muscle; glucocorticoid; corticosteroid; preterm
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Funding
- Robert Wood Johnson Foundation
- UTHSCSA CTSA [UL1RR025767]
- American Diabetes Association
- National Institutes of Health [HL52636, AG030979]
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We hypothesize that prenatal exposure to glucocorticoids (GCs) negatively alters the insulin signal transduction pathway and has differing effects on the fetus according to gestational age (GA) at exposure. Twenty-three fetal baboons were delivered from 23 healthy, nondiabetic mothers. Twelve preterm (0.67 GA) and 11 near-term (0.95 GA) baboons were killed immediately after delivery. Half of the pregnant baboons at each gestation received two doses of i.m. betamethasone 24 h apart (170 mg/kg) before delivery, while the other half received no intervention. Vastus lateralis muscle was obtained from postnatal animals tomeasure the protein content and gene expression of insulin receptor beta (IRb; INSR), IRb Tyr 1361 phosphorylation (pIRb), IR substrate 1 (IRS1), IRS1 tyrosine phosphorylation (pIRS1), p85 subunit of PI3-kinase, AKT (protein kinase B), phospho-AKT Ser473 (pAKT), AKT1, AKT2, and glucose transporters (GLUT1 and GLUT4). Skeletal muscle from preterm baboons exposed to GCs had markedly reduced protein content of AKTand AKT1 (respectively, 73 and 72% from 0.67 GA control, P! 0.001); IRb and pIRb were also decreased (respectively, 94 and 85%, P! 0.01) in themuscle of premature GCexposedfetusesbut not intermfetuses. GLUT1andGLUT4tendedto increasewithGCexposure in preterm animals (PZ0.09), while GLUT4 increased sixfold in term animals after exposure to GC (P! 0.05). In conclusion, exposure to a single course of antenatal GCs during fetal life alters the insulin signaling pathway in fetal muscle in a manner dependent on the stage of gestation.
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